Coincidence correction circuit

ABSTRACT

For use with a particle counting system, circuitry for correction for the coincident passage of multiple particles through a metering aperture. A read-only memory is employed to store data representing predetermined counting levels at which corrections are to be made during a counting sequence and at such counting levels a correction pulse is added to the then measured particle count to provide an output count which is continuously corrected in accordance with the actual nature of the accumulating coincidence error.

O United States Patent [111 3,864,551

Oefinger [4 Feb. 4, 1975 COINCIDENCE CORRECTION CIRCUIT [75] Inventor:Arthur Oefinger, Stratford, Conn. i gzg iys rgzgzg m Jr [73] Assignee:General Science Corp., Bridgeport, Attorney, Agent, or Fhm-WeingarteniMaxham &

COIIH- Schurgin [22] Filed: Mar. 1, 1974 [21] Appl. NO.Z 447,530 [57]ABSTRA CT For use with a particle counting system, clrcultry forcorrection for the coincident passage of multiple parti- [52] 235/92235/92 235/92 cles through a metering aperture. A read-only memory324/71 CP is employed to store data representing predetermined [51] hit.Cl. G06!!! 11/00, H03k 21/34 counting levels at which corrections are tobe made [58] Field of Search 235/92 PC, 92 PL; during a countingSequence and at Such counting 324/71 CP els a correction pulse is addedto the then measured particle count to provide an output count which is[56] References C'ted continuously corrected in accordance with theactual UNITED STATES PATENTS nature of the accumulating coincidenceerror.

3,209,130 9/1965 Schmidt 235/92 PL 3,686,665 8/1972 Elias et al. 235/92PL 11 3 Draw ADDRESS REGISTER MULTI- PLEXER CONTROL CORRECTED COUNTPATENTED FEB 4|975 7 /2O CONDUCTIVITY Y J r 1 I PUMP I w v 11 W VOLUME'WASTE I I METERING ,VESSEL' v /"14 -12 70 28 L i 2 CONTROLS 'Y' f LOGICCOUNT 24g CIRCUITRY DISPLAY g 1.

/-34, MV INPUT I 32 COUNT MV CLK 44 46V 40 ,2, 38 V NAND G ADDRESS ROMMULTI- CORRECTED REGISTER ,PLExER 42 OR COUNT NAND Flg. 2. E

.coNTRoL @3 TO NAND GATE TO NAND GATE I COINCIDENCE CORRECTION CIRCUITFIELD OF THE INVENTION incidence error caused by coincident passage ofmultiple particles through a metering aperture,

BACKGROUND OF THE INVENTION Systems are known for counting blood cellsor other particles suspended in a liquid, a preferred system being shownin US. Pat. No. 27,902 assigned to the assignee of the presentinvention. In such a system electrical pulses are provided in responseto the passage of particles through a metering aperture of a transduceror conductivity cell which is disposed within a fluid path and haselectrodes on respective opposite sides of the aperture. The impedanceof the fluid path is materially altered by the presence of a particlewithin the aperture, resulting in production of electrical pulsescorresponding to the number of particles passing through the apertureand which pulses are electronically counted to provide an outputindication of particle count. A known volume of particle-containingliquid is usually metered by appropriate means to provide a particlecount for a known volume of liquid.

During operation an error known as coincidence error arises by reason ofthe coincident or nearly coincident passage of more than one particlethrough the metering aperture and which is sensed as a signle particle,with the result that the number of measured particles is lower than theactual particle count for a given quantity of sample liquid. The erroris statistically predictable for known particle concentrations andmetering aperture sizes, and correction charts are usually employed toderive a corrected particle count. The use of a correction chart is, ofcourse, time consuming and itself productive of error due to misreadingof the chart or erroneous copying of correction numbers. Automated meanshave been proposed for providing a corrected particle count, one suchmeans being shown in US. Pat. No. 3,626,164 in which differentcorrections are applied to the measured count after specific numbers ofcounts as determined by a plurality of decade counters to provide anoutput count which is corrected somewhat for coincidence error.Continuous correction throughout the counting range is not provided noris the correction in precise conformity to the real error which arises.

SUMMARY OF THE INVENTION In accordance with the present invention acoincidence correction circuit provide correction which is substantiallyin conformity with the actual error which arises in a particle countingsystem and which provides effectively continuous correction for sucherror to produce a corrected count throughout the entire counting range.At predetermined counting levels, representations of which are stored ina read-only memory, a correction pulse is added to the accumulatingmeasured particle count to correct the count in accordance with thestatistically determined actual nature of the accumulating error.

DESCRIPTION OF THE DRAWINGS The invention will be more fully understoodfrom the 2 following detailed description taken in conjunction with theaccompanying drawings, in which:

FIG. 1 is a schematic representation of a particle counting system inwhich the invention is useful; 3

FIG. 2 is a block diagram representation of a coincidence correctioncircuit according to the invention; and

FIG. 3 is a block diagram representation of a typical implementation ofthe circuitry of FIG. 2.

DETAILED DESCRIPTION OF THE INVENTION A particle counting system inwhich the invention is useful is shown diagrammatically in FIG. 1 andwhich itself is the subject of US. Pat. No. 27,902. This system includesa conductivity cell or transducer I0 having a metering aperture andelectrodes therein for providing electrical pulses on output line 12corresponding and in response to particles passing through the aperturethereof. Particle-containing liquid is drawn from a sample containerinto cell 10 via an input tube 14 and exits through a-tube 16 whichterminates in a waste vessel 18 to which is also coupled to pump 20.Pump 20 provides a negative pressure for drawing sample liquid throughcell 10 for analysis during a counting run. The output pulses from cell10 are applied to an amplifier 22, the output of which is coupled tologic circuitry 24 which processes the received pulses to provide anoutput signal to a count display 26 which visually indicates theparticle count for a given quantity of sample liquid. The samplequantity being analyzed is determined by volume metering means 28 whichsenses a known quantity of sample liquid flowing through tube 16 andprovides electrical start and stop signals to logic circuitry 24 todefine a counting interval within which a particle count is accumulatedfor display. Appropriate controls 30 are coupled to logic circuitry 24for operation thereof.

The passage of a particle through the metering aperture of conductivitycell 10 alters the impedance of the fluid path within the cell, causingthe provision of a cor responding'electrical pulse which is thenprocessed for accumulating a particle count. In practice, two or moreparticles can simultaneously pass through the metering aperture, givingrise to the production of a single pulse which erroneously denotes thepassage of a single particle. The error occasioned by such multipleparticle passages is termed coincidence error and produces a lower thantrue count. The coincidence error is statistically predictable for knownaperture sizes and concentrations of sample liquid and the correction isrequired at predetermined counts of a sequence of measured counts. Thepresent invention provides the circuitry for augmenting the measuredcount throughout a counting run by addition of correction pulsesnecessary to provide a corrected output count actually representative ofthe true count.

The novel circuitry is shown in FIG. 2 and includes first and secondmultivibrators 32 and 34, each of which receive the electrical pulsesrepresentative of measured particle count. Multivibrator 32 providesoutput pulses as a clock signal to an address register 36 and alsoprovides its output pulses as one input of OR gate 38, the output ofwhich gate is the corrected count. The output pulses from multivibrator34 are applied as one input to NAND gates 40 and 42, the outputs ofwhich are applied to respective inputs of OR gate 38. Address register36 has its output lines coupled to the inputs of a read-only memory 44,the output of which is coupled to a multiplexer 46 which provides firstand second output signals to gates 40 and 42 respectively. A controlsignal is applied from a suitable source to an input of gate 40 and viaan inverter 48 to an input of gate .42. The multivibrators 32 and 34typically are one shot multivibrators, multivibrator 32 being triggeredon the trailing edge of an input pulse while multivibrator 34 istriggered on leading edge of the input pulse. As a result, apredetermined time delay is provided between the respective outputpulses from the multivibrators sufficient to permit signal processingfor providing correction data.

The address register 36 provides an output code corresponding to thenumber of clock pulses applied thereto and which code addresses aread-only memory 44 which has stored therein data representative of thecoincidence points of a correction chart at which additional pulses areto be added to a measured count. At the addresses of the stored data,memory 44 provides an output code to multiplexer 46 which produces anoutput signal to gate 40 or 42 to cause an additional pulse to be addedto the measured count for correction. When the invention is employed ina system for counting different types of particles such as red bloodcells, white blood cells or platelets, the coincidence error isdifferent due to the different dilutions and size of apertures required.The read-only memory 44 can have stored therein correction data fordifferent needed corrections. For example, memory 44 can storecorrection data for multiple sets of data. Only one NAND gate 40 or 42is operative in accordance with the value of the control signal appliedthereto depending upon the type of particles, say red cells or whitecells, being counted.

In operation, pulses provided by a particle counting system transducerand of a number representative of measured particle count are applied tomultivibrator 32 which provides corresponding output pulses to OR gate38 which, in turn, provides output pulses for subsequent processing anddisplay. The input pulses are also applied to multivibrator 34 whichprovides corresponding pulses to an input of NAND gates 40- and 42. Acontrol signal is applied to one or the other of gates 40 and 42 toenable a selected one of these gates in accordance with the type ofblood cells being counted. For example, during a red blood cell countingrun an enabling signal can be applied to gate 40 while gate 42 isenabled during a white blood cell counting run. In the illustratedembodiment the control signal is a logic level applied to gate 40 andthe inverse of which is applied to gate 42. Thus, a control input oflogic level one will provide a one level'to gate 40 and a zero level togate 42. Alternatively, a control level of zero will pro-' vide a zerolevel at gate 40 and a one level at gate 42.

Address register 36 is operative in response to the clock pulsesprovided by multivibrator 32, and which in turn is representative of theinput pulses to provide a parallel output code to sequentially addressmemory 44 in accordance with successive values of the received particlecount. At selected addresses of the data stored in memory 44, the memoryprovides an output code to multiplexer 46 which in turn provides anoutput signal to gates 40 and 42. The enabled one of gates 40 or 42,upon receipt of a signal from multiplexer 46 and multivibrator 34,provides an output pulse to OR gate 38 which provides a correction pulsefor addition to the then count.

Read-only memory 44 is typically a semiconductor memory programmed inaccordance with the corrections needed for a particular aperture sizeand sample liquid dilution and which in the illustrated embodiment -hasstored data for both red cell and white cell coincidence correction. Themultiplexer 46 will decode the memory output codes provided for both redcell and white cell coincidence correction, but, as described above,only the intended correction information is employed as determined bythe enablement of gate 40 or 42 depending upon whether red or whitecells are being counted.

The novel circuitry is typically implemented in integrated circuit formand with the read-only memory programmed in accordance with theconfiguration of a particular metering aperture employed in thetransducer ofa particle counting system and the dilution ratios of thesample liquid.

A preferred implementation of the novel circuit is shown in FIG. 3wherein the address register 36 is comprised of three integrated circuitbinary counters 50, 52 and 54, such as Texas Instrument type 7493counters. The clock signal from multivibrator 32 is applied to the clockinput of counter 50 and the D output is coupled to the clock input ofcounter 52 while the D output thereof is, in turn, coupled to the inputof counter 54. The A and B outputs of counter 50 are coupled to therespective control inputs of multiplexing gates 56 and 58 which gatescomprise the multiplexer 46 of FIG. 2. Gates 56 and 58 are typicallyTexas Instruments type 74153 multiplexers. The C and D outputs ofcounter 50 are applied as inputs to read-only memory 44 while the fouroutputs of counter 52 and the A and B outputs of counter 54 are alsoapplied as inputs to memory 44.

From the foregoing, it will be appreciated that the invention providescorrection for coincidence error in accordance with the actual erroraccumulating throughout a particle counting run and on an effectivelycontinuous basis. The invention in actual implementation may take avariety of forms to suit specific constructional and operationalrequirements without departing from the spirit and true scope of theinvention. Accordingly, it is not intended to limit the invention bywhat has been particularly shown and described, except as indicated inthe appended claims.

What is claimed is:

1. In a particle counting system including a transducer having anaperture through which particlecontaining liquid is caused to flow andmeans for generating electrical pulses in response to particles passingthrough said aperture, circuitry for providing correction for thecoincident passage of multiple particles through said aperture, saidcircuitry comprising:

means for providing first pulses in response to said electrical pulsesand representative of measured particle count;

means for providing second pulses in response to said electrical pulses;

memory means containing data representing predetermined particle countsat which correction is to occur; address means operative in response tosaid first pulses to address said memory means to cause the provision ofparallel output codes therefrom;

multiplexer means operative in response to said parallel output codes toprovide at least one gating signal;

first gate means operative in response to said at least one gatingsignal and to said second pulses to provide a correction pulse; and

second gate means operative in response to said first pulses and saidcorrection pulse to provide output pulses representative of a correctedparticle count.

2. The invention according to claim 1 wherein said first pulse andsecond pulse providing means each include a multivibrator operative toprovide an output pulse in response to a corresponding input pulsethereto.

3. The invention according to claim 2 wherein said multivibratorproviding said first pulses is triggered on the trailing edge of saidelectrical pulses and said multivibrator providing said second pulses istriggered on the leading edge of said electrical pulses, thereby toprovide a predetermined time delay between respective first and secondpulses sufficient for coincidence correction processing.

4. The invention according to claim 1 wherein said memory means includesa read-only memory programmed with said data representing predeterminedparticle counts at which correction is to occur for a particularlyconfigured metering aperture and dilution ratio of thepartical-containing liquid.

5. The invention according to claim 4 wherein said address meansincludes an address register providing successive address codes inresponse to successive first pulses for addressing said read-only memoryin accordance with the number of first pulses received.

6. The invention according to claim 4 wherein said first gate meansincludes a NAND gate coupled to said multiplexer means and to saidsecond pulse providing means;

and wherein said second gate means includes an OR gate coupled to saidNAND gate and to said first pulse providing means.

7. The invention according to claim 1 wherein said memory means is aread-only memory containing data representative of said predeterminedparticle counts for different types of particles;

and wherein said first gate means includes first and second NAND gatesoperative to receive said second pulses and gating signals from saidmultiplexer means; and

enabling means coupled to said NAND gates and operative to enable aselected one thereof in accordance with the type of particles beingcounted.

8. The invention according to claim I wherein said memory means is aread-only memory containing data representative of said predeterminedparticle counts for different types of particles;

said multiplexer means is operative-in response to said output codesfrom said read-only memory to provide at least one gating signal foreach of said different types of particles; and said first gate meansincludes first and second gates operative to receive respective ones ofsaid gating signals and said second pulses; and

enabling means coupled to said first and second gates and operative toenable a selected one thereof in accordance with the type of particlesbeing counted.

9. The invention according to claim 8 wherein said second gate meansincludes an OR gate coupled to said first and second gates and to saidfirst pulse providing means.

10. The invention according to claim 9 wherein said enabling meansincludes:

a source of control signals;

means coupling said source to said first gate; and

inverter means coupling said source to said second gate.

ll. The invention according to claim 1 wherein said memory meansincludes a read-only memory programmed with said data representingpredetermined particle counts at which correction is to occur, said databeing statistically determined in accordance with the dilution ratio ofthe particle-containing liquid and the transducer aperture size.

1. In a particle counting system including a transducer having anaperture through which particle-containing liquid is caused to flow andmeans for generating electrical pulses in response to particles passingthrough said aperture, circuitry for providing correction for thecoincident passage of multiple particles through said aperture, saidcircuitry comprising: means for providing first pulses in response tosaid electrical pulses and representative of measured particle count;means for providing second pulses in response to said electrical pulses;memory means containing data representing predetermined particle countsat which correction is to occur; address means operative in response tosaid first pulses to address said memory means to cause the provision ofparallel output codes therefrom; multiplexer means operative in responseto said parallel output codes to provide at least one gating signal;first gate means operative in response to said at least one gatingsignal and to said second pulses to provide a correction pulse; andsecond gate means operative in response to said first pulses and saidcorrection pulse to provide output pulses representative of a correctedparticle count.
 2. The invention according to claim 1 wherein said firstpulse and second pulse providing means each include a multivibratoroperative to provide an output pulse in response to a correspondinginput pulse thereto.
 3. The invention according to claim 2 wherein saidmultivibrator providing said first pulses is triggered on the trailingedge of said electrical pulses and said multivibrator providing saidsecond pulses is triggered on the leading edge of said electricalpulses, thereby to provide a predetermined time delay between respectivefirst and second pulses sufficient for coincidence correctionprocessing.
 4. The invention according to claim 1 wherein said memorymeans includes a read-only memory programmed with said data representingpredetermined particle counts at which correction is to occur for aparticularly configured metering aperture and dilution ratio of thepartical-containing liquid.
 5. The invention according to claim 4wherein said address means includes an address register providingsuccessive address codes in response to successive first pulses foraddressing said read-only memory in accordance with the number of firstpulses received.
 6. The invention according to clAim 4 wherein saidfirst gate means includes a NAND gate coupled to said multiplexer meansand to said second pulse providing means; and wherein said second gatemeans includes an OR gate coupled to said NAND gate and to said firstpulse providing means.
 7. The invention according to claim 1 whereinsaid memory means is a read-only memory containing data representativeof said predetermined particle counts for different types of particles;and wherein said first gate means includes first and second NAND gatesoperative to receive said second pulses and gating signals from saidmultiplexer means; and enabling means coupled to said NAND gates andoperative to enable a selected one thereof in accordance with the typeof particles being counted.
 8. The invention according to claim 1wherein said memory means is a read-only memory containing datarepresentative of said predetermined particle counts for different typesof particles; said multiplexer means is operative in response to saidoutput codes from said read-only memory to provide at least one gatingsignal for each of said different types of particles; and said firstgate means includes first and second gates operative to receiverespective ones of said gating signals and said second pulses; andenabling means coupled to said first and second gates and operative toenable a selected one thereof in accordance with the type of particlesbeing counted.
 9. The invention according to claim 8 wherein said secondgate means includes an OR gate coupled to said first and second gatesand to said first pulse providing means.
 10. The invention according toclaim 9 wherein said enabling means includes: a source of controlsignals; means coupling said source to said first gate; and invertermeans coupling said source to said second gate.
 11. The inventionaccording to claim 1 wherein said memory means includes a read-onlymemory programmed with said data representing predetermined particlecounts at which correction is to occur, said data being statisticallydetermined in accordance with the dilution ratio of theparticle-containing liquid and the transducer aperture size.